7K3R

Cryo-EM structure of AIM2-PYD filament

Summary for 7K3R

• Entry DOI: 10.2210/pdb7k3r/pdb
• EMDB information: 22656
• Descriptor: Interferon-inducible protein AIM2 (1 entity in total)
• Functional Keywords: inflammasome, aim2 filament, helical reconstruction, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 21
• Total formula weight: 284101.76

Authors

Zheng, W.,Matyszewski, M.,Sohn, J.,Egelman, E.H. (deposition date: 2020-09-12, release date: 2021-05-26, Last modification date: 2024-03-06)

Primary citation

Matyszewski, M.,Zheng, W.,Lueck, J.,Mazanek, Z.,Mohideen, N.,Lau, A.Y.,Egelman, E.H.,Sohn, J.
Distinct axial and lateral interactions within homologous filaments dictate the signaling specificity and order of the AIM2-ASC inflammasome.
Nat Commun, 12:2735-2735, 2021

PubMed Abstract: Inflammasomes are filamentous signaling platforms integral to innate immunity. Currently, little is known about how these structurally similar filaments recognize and distinguish one another. A cryo-EM structure of the AIM2 filament reveals that the architecture of the upstream filament is essentially identical to that of the adaptor ASC filament. In silico simulations using Rosetta and molecular dynamics followed by biochemical and cellular experiments consistently demonstrate that individual filaments assemble bidirectionally. By contrast, the recognition between AIM2 and ASC requires at least one to be oligomeric and occurs in a head-to-tail manner. Using in silico mutagenesis as a guide, we also identify specific axial and lateral interfaces that dictate the recognition and distinction between AIM2 and ASC filaments. Together, the results here provide a robust framework for delineating the signaling specificity and order of inflammasomes.

PubMed: 33980849
DOI: 10.1038/s41467-021-23045-8

Experimental method

ELECTRON MICROSCOPY (3.2 Å)